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RU2012132218A - Соединения и фармацевтические композиции для лечения вирусных инфекций - Google Patents

Соединения и фармацевтические композиции для лечения вирусных инфекций Download PDF

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RU2012132218A
RU2012132218A RU2012132218/04A RU2012132218A RU2012132218A RU 2012132218 A RU2012132218 A RU 2012132218A RU 2012132218/04 A RU2012132218/04 A RU 2012132218/04A RU 2012132218 A RU2012132218 A RU 2012132218A RU 2012132218 A RU2012132218 A RU 2012132218A
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Жан-Пьер Соммадосси
Жилль ГОССЕЛЭН
Клер ПЬЕРРА
Кристиан ПЕРИГО
Сюзанн ПЕЙРОТТ
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Айденикс Фармасьютикалз, Инк.
Сантр Насьональ Де Ля Решерш Сьентифик
Л'Юниверсите Монпелье Ii
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Abstract

1. Соединение формулыили его фармацевтически приемлемая соль, стереоизомерная, таутомерная или полиморфная форма, в котором;Rпредставляет собой необязательно замещенный алкил, алкенил, алкинил, арил, арилалкил, циклоалкил, циклоалкенил, гидроксиалкил, амино, гетероциклил или гетероарил;Rи Rвыбирают следующим образом:i) Rи Rкаждый независимо представляют собой водород или необязательно замещенный алкил, карбоксиалкил, гидроксиалкил, гидроксиарилалкил, ацилоксиалкил, аминокарбонилалкил, алкоксикарбонилалкил, арил, арилалкил, циклоалкил, гетероарил или гетероциклил; илиii) Rи Rвместе с атомом азота, на который они замещены, образуют гетероциклическое или гетероарильное кольцо, имеющее от 3 до 7 членов; иRвыбран из группы состоящей из рибавирина, вирамидина, валопицитабина, PSI-6130, МК-0608, резиквимода, целгосивира, ламивудина, энтекавира, телбивудина, рацивира, эмтрицитабина, клевудина, амдоксовира, тенофовира и адефовира.2. Соединение по п.1, имеющее формулу:или его фармацевтически приемлемая соль, стереоизомерная, таутомерная или полиморфная форма.3. Соединение по п.1, имеющее формулу:или его фармацевтически приемлемая соль, стереоизомерная, таутомерная или полиморфная форма.4. Соединение по п.1, имеющее формулу:или его фармацевтически приемлемая соль, стереоизомерная, таутомерная или полиморфная форма.5. Соединение по п.1, имеющее формулу:илиRпредставляет собой водород, метил или метокси;Rнезависимо представляет собой H, карбамил, линейный, разветвленный или циклический алкил; ацил; СО-алкил, СО-арил, СО-алкоксиалкил, CO-арилоксиалкил, СО-замещенный арил, сложный эфир сульфоната, липид, аминокислота; аминокислотный остаток

Claims (19)

1. Соединение формулы
Figure 00000001
или его фармацевтически приемлемая соль, стереоизомерная, таутомерная или полиморфная форма, в котором;
Ry представляет собой необязательно замещенный алкил, алкенил, алкинил, арил, арилалкил, циклоалкил, циклоалкенил, гидроксиалкил, амино, гетероциклил или гетероарил;
Ra и Rb выбирают следующим образом:
i) Ra и Rb каждый независимо представляют собой водород или необязательно замещенный алкил, карбоксиалкил, гидроксиалкил, гидроксиарилалкил, ацилоксиалкил, аминокарбонилалкил, алкоксикарбонилалкил, арил, арилалкил, циклоалкил, гетероарил или гетероциклил; или
ii) Ra и Rb вместе с атомом азота, на который они замещены, образуют гетероциклическое или гетероарильное кольцо, имеющее от 3 до 7 членов; и
R1 выбран из группы состоящей из рибавирина, вирамидина, валопицитабина, PSI-6130, МК-0608, резиквимода, целгосивира, ламивудина, энтекавира, телбивудина, рацивира, эмтрицитабина, клевудина, амдоксовира, тенофовира и адефовира.
2. Соединение по п.1, имеющее формулу:
Figure 00000002
или его фармацевтически приемлемая соль, стереоизомерная, таутомерная или полиморфная форма.
3. Соединение по п.1, имеющее формулу:
Figure 00000003
или его фармацевтически приемлемая соль, стереоизомерная, таутомерная или полиморфная форма.
4. Соединение по п.1, имеющее формулу:
Figure 00000004
или его фармацевтически приемлемая соль, стереоизомерная, таутомерная или полиморфная форма.
5. Соединение по п.1, имеющее формулу:
Figure 00000005
Figure 00000006
или
Figure 00000007
Rd представляет собой водород, метил или метокси;
RL независимо представляет собой H, карбамил, линейный, разветвленный или циклический алкил; ацил; СО-алкил, СО-арил, СО-алкоксиалкил, CO-арилоксиалкил, СО-замещенный арил, сложный эфир сульфоната, липид, аминокислота; аминокислотный остаток, или углевод;
или его фармацевтически приемлемая соль, стереоизомерная, таутомерная или полиморфная форма.
6. Соединение по п.1, имеющее формулу:
Figure 00000008
или его фармацевтически приемлемая соль, стереоизомерная, таутомерная или полиморфная форма.
7. Соединение по любому из пп.1-5, в котором Ry является замещенным алкилом и Ra и Rb независимо представляют собой водород, алкил, замещенный алкил, бензил или замещенный бензил.
8. Соединение по п.7, в котором Ry является гидроксиалкилом или аминоалкилом.
9. Соединение по п.1, в котором Ry представляет собой -ORC, -C(RC)3 или -NHRC, где каждый из RC независимо представляет собой алкил, замещенный алкил, арил или замещеннвй арил; и Ra и Rb независимо представляют собой водород, алкил, замещенный алкил, бензил или замещенный бензил.
10. Соединение по п.1, в котором Ra и Rb независимо представляют собой водород, бензил или замещенный алкил.
11. Соединение по п.1, представляющее собой
Figure 00000009
или
Figure 00000010
12. Фармацевтическая композиция, содержащая соединение по любому из пп.1-11 и фармацевтически приемлемый наполнитель, носитель или разбавитель.
13. Композиция по п.12, в котором композиция представляет собой рецептуру для перорального приема.
14. Применение соединения согласно любому из пп.1-11, для лечения организма-хозяина, инфицированного флавивирусом или вирусом гепатита B.
15. Применение по п.14 для лечения организма-хозяина, инфицированного вирусом гепатита B.
16. Применение по п.14 для лечения организма-хозяина, инфицированного вирусом гепатита C.
17. Применение по п.14, в котором указанное соединение или фармацевтическую композицию вводят в комбинации или чередовании со вторым противовирусным средством, необязательно выбираемым из группы, состоящей из интерферона, рибавирина, интерлейкина, ингибитора протеазы NS3, ингибитора цистеин-протеазы, фенантренхинона, производного тиазолидина, тиазолидина, бензанилида, ингибитора геликазы, ингибитора полимеразы, нуклеотидного аналога, глиотоксина, церуленина, антисмыслового олигодезоксинуклеотида фосфоротиоата, ингибитора IRES-зависимой трансляции и рибозима; или в котором соединение или его фармацевтически приемлемую соль или стереоизомер вводят в комбинации или чередовании со вторым противовирусным средством, необязательно выбираемым из группы, состоящей из интерферона, рибавирина, интерлейкина, ингибитора протеазы NS3, ингибитора цистеин-протеазы, фенантренхинона, производного тиазолидина, тиазолидина, бензанилида, ингибитора геликазы, ингибитора полимеразы, нуклеотидного аналога, глиотоксина, церуленина, антисмыслового олигодезоксинуклеотида фосфоротиоата, ингибитора IRES-зависимой трансляции и рибозима, причем необязательно второе средство выбирают из группы, состоящей из пегилированного интерферона-альфа 2a, интерферона альфакон-1, интерферона природного происхождения, альбуферона, интерферона-бета 1a, интерферона омега, интерферона альфа, интерферона гамма, интерферона тау, интерферона дельта и интерферона γ-1b.
18. Применение по п.14, в котором организмом-хозяином является человек.
19. Применение по п.14, в котором при указанном введении существенное количество указанного соединения или фармацевтической композиции направленно поступает в печень указанного организма-хозяина.
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